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US3254094A - 3-imino-2, 1-benzisothiazoles - Google Patents

3-imino-2, 1-benzisothiazoles Download PDF

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US3254094A
US3254094A US405251A US40525164A US3254094A US 3254094 A US3254094 A US 3254094A US 405251 A US405251 A US 405251A US 40525164 A US40525164 A US 40525164A US 3254094 A US3254094 A US 3254094A
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D275/00—Heterocyclic compounds containing 1,2-thiazole or hydrogenated 1,2-thiazole rings
    • C07D275/04—Heterocyclic compounds containing 1,2-thiazole or hydrogenated 1,2-thiazole rings condensed with carbocyclic rings or ring systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
    • C07C51/08—Preparation of carboxylic acids or their salts, halides or anhydrides from nitriles

Definitions

  • R represents hydrogen, halogen of atomic weight less than 80 or trifluoromethyl, preferably the substituent is in the 5- or 6-position;
  • R represents hydrogen, lower alkyl or phenyl
  • R represents hydrogen or lower alkyl.
  • lower alkyl Where used herein signifies aliphatic groups of from one to four, preferably one to two, carbon atoms.
  • a preferred compound is S-imino-l,3-dihydro-5-trifiuoromethyl-2,1-benzisothiazole.
  • This invention also includes salts of the above defined bases formed with nontoxic organic and inorganic acids.
  • Such salts are easily prepared by methods known to the art.
  • the base is reacted with either the calculated amount of organic or inorganic acid in aqueous miscible solvent, such as acetone or ethanol, with isolation of the salt by concentration and cooling or an excess of the acid in aqueous immiscible solvent, such 'as ethyl ether or chloroform, with the desired salt separating directly.
  • aqueous miscible solvent such as acetone or ethanol
  • organic salts are those with ma-leic, hexamic, furnaric, benzoic, ascorbic, pamoic, succinic, bismethylenesalicylic, methanesulfonic, ethanedisulfonic, acetic, propionic, tartaric, salicylic, citric, gluconic, lactic, malic, mandelic, cinnamic, citraconic, aspartic, stearic, palmitic, itaconic, glycolic, p-aminobenzoic, glutamic, benzenesulfonic and the-ophylline acetic acids as well as with the 8-halotheophyllines, for example, 8-bromotheophylline.
  • Exemplary of such inorganic salts are those with hydrochloric, hydrobromic, hydroiodic, sulfuric, sulfamic, phosphoric and nitric acids.
  • these salts may also be prepared by the classical method of double decomposition of .appropri the salts which is well-known to the art.
  • a 2- amino-benzthioamide as shown in Formula II is ring closed to form the 2,1-benzisothiazole using a mild oxidizing agent, for example potassium triiodide or a halogen: iodine, bromine or chlorine.
  • a mild oxidizing agent for example potassium triiodide or a halogen: iodine, bromine or chlorine.
  • potassium triiodide the reaction is advantageously carried out in an aqueous system, for example aqueous alcoholic solution such as methanol or ethanol at from 0-80 C., preferably at ambient or room temperature, for from 30 minutes to several hours.
  • reaction product is isolated as the hydroiodide salt of the 2,1-benzoisothiazole and if desired, the salt is treated with a weak inorganic or organic base to yield the benzisothiazole free base.
  • a weak inorganic or organic base to yield the benzisothiazole free base.
  • of Formula I is hydrogen, sodium carbonate solution is employed to generate the free base. Further reaction with acids yields other salts as described hereinabove.
  • the above reaction is advantageously carried out in a dilute solution using a suitable solvent which is unreactive toward the oxidizing agent, such as for example acetic acid, in a similar temperature range.
  • a suitable solvent which is unreactive toward the oxidizing agent, such as for example acetic acid
  • the Z-aminobenzthioamide starting materials used as described above are either known or are prepared by one of several procedures. to prepare the N-unsubstituted amido compounds of Formula II above:
  • an anthanilonitrile is reacted with a mixture of liquid ammonia and gaseous hydrogen sulfide (ammonium sulfide) in an inert solvent such as Cellosolve, under pressure, for from four to eight hours to give upon workup the benzthioamide compound.
  • an inert solvent such as Cellosolve
  • R and R are as defined hereinabove and R is lower alkyl.
  • a 2-chlorobenzoyl halide (prepared from the corresponding carboxylic acid as set forth in the examples hereinbelow) is treated with a lower alkyl amine to yield the N-loweralkyl-Z-chlorobenza-mide which is reacted with ammonia or an amine in the presence of copper powder and a copper salt.
  • the resulting N-lower alkyl-2-aminobenzamide is converted to the corresponding benzthioamide by the action of phosphorus pentasulfide.
  • Example 1 A mixture of 648 g. of 4-chloro-3-cyanobenzotrifluoride, one liter of liquid ammonia, 4 g. cuprous chloride and 4 g. of copper powder is heated at 115-120 C. in a closed reactionvessel. The pressure climbs to 1030 pounds. The reaction vessel is washed with isopropanol and the filtered catalyst is washed with isopropanol and ether. The filtrate is concentrated and distilled to yield 5-trifluoromethylanthranilonitrile, B.P. 95-115 C./0.4 0.7 mm. The product recrystallizes from benzene and cyclohexane to melt at 7274 C.
  • Liquid ammonia (about ml.) is dissolved in 75 ml. of Cellosolve and gaseous hydrogen sulfide is passed in for 20 minutes at 5 C.
  • a solution of 5.0 g. of the above 5-trifluoromethylanthrani-lonitrile in 10 ml, of Cellosolve is added and the mixture is placed in a glass bomb which is then heated in a steam bath with occasional shaking. After four hours the bomb is cooled and the contents is concentrated to dryness under reduced pressure. The residue is recrystallized from benzene-heptane to give 2 amino 5 trifluoromethylbenzthioamide, M.P. 119121 C.
  • the above thioamide (2.05 g.) is dissolved in a mixture of 50 ml. of methanol and 50 ml. of water.
  • a solution of g. of potassium iodide and 2.36 g. of iodine in 50 ml. of water is added dropwise with stirring to the thioamide solution.
  • the temperature is kept below 15 C.
  • the mixture is stirred for two hours, then filtered to give 3- imino-1,3-dihydro 5 trifluoromethyl-Z,l-benzisothiazole hydroiodide.
  • the free base is obtained by treating a methanolic solution of the hydroiodide with excess aqueous sodium carbonate solution. After recrystallization from benzene the free base product melts at 202- 203 C.
  • Example 2 To a solution of 6.0 g. of 2-aminobenzthioamide in 250 ml. of 50% aqueous methanol is added with stirring, a solution of 81 g. of potassium iodide and 10.0 g. of iodine in 250 ml. of water. The temperature is kept below 10 C. The mixture is stirred for one hour and filtered to give 3-imino-l,3-dihydro 2,1 benzisothiazole hydroiodide. methanolic solution of the hydroiodide with excess aqueous sodium carbonate solution. After recrystallization from ethanol the free base melts at 169.5171.5 C.
  • Example 3 To 21 g. of dry pyridine is added slowly with stirring, 23 g. of cuprous cyanide. The mixture rapidly solidifies and is then heated to 125 C. Excess pyridine is boiled off and the temperature decreased to 110 C. With stirring, 48 g. of 3-amino-4-bromobenzotrifiuoride is added slowly and the mixture heated to 165170 C. This temperature is maintained for 75 minutes and then the reac tion mixture is cooled to 90 C. A concentrated solution of sodium cyanide (75 .g. in 75 ml; of water) is added, followed by 250 ml. of benzene. The mixture is stirred for one hour and the separated benzene layer is washed with water, dried and evaporated. The residue is distilled at 122127 C. and 7.0 mm. to give 4-trifluoromethylanthranilonitrile which solidifies, melting at 86-89 C.
  • the free base is obtained by treating a 4 Example 4 trifluoromethylanthranilonitrile which solidified, M.P. 91-
  • Example 5 A mixture of g. of 4-chloro-3-cyanobenzotrifluoride, 70 g. of sodium hydroxide, 200 ml. of ethanol and 700 ml. of water is stirred at reflux for six and one-half hours. The solution is cooled, filtered and the filtrate extracted with ether and then benzene. The aqueous layer is treated with charcoal, refiltered and then acidified with excess hydrochloric acid to precipitate 2-chloro-5-trifluoromethylbenzoic acid, M.P. 92.5-95 C. This benzoic acid (108 g.) is stirred with 250 ml. of thionyl chloride for-one hour and refluxed for two hours. The excess thionyl chloride is distilled at the water pump and the residue distilled to give 2-chloro-S-trifluoromethylbenzoyl chloride, B.P. 113117 C./ca. 20 mm.
  • Example 6 Following the general procedure of Example 1, 4.1 g. of 5-chloroanthranilonitrile is reacted with ammonium sulfide (ammonia and hydrogen sulfide) in 75 ml. of Cellosolve under pressure to give 2-amino-5-chlorobenzthioamide.
  • the thioamide thus prepared is reacted in aqueous methanol solution with an equimolar amount of iodine and an excess of potassium iodide.
  • the reaction mixture is stirred at room temperature for one hour and then filtered to give 3-imino-1,3-dihydro-5-chloro-2,1- benzisothiazole hydroiodide.
  • the free base is obtained by treating a methanolic solution of the hydroiodide with excess aqueous sodium carbonate solution.
  • a chemical compound of the class consisting of a free base and its nontoxic, pharmaceutically acceptable acid addition salts, said free base having the formula:
  • R is a member selected from the group consisting of hydrogen, halogen of atomic weight less than 80 and trifiuoromethyl; R is a member selected from the group consisting of hydrogen, lower alkyl of from 1 to 4 carbon atoms and.
  • R is a member selected from the group consisting of hydrogen and lower alkyl of from 1 to 4 carbon atoms.
  • R R and R are as defined above.

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Oil, Petroleum & Natural Gas (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Thiazole And Isothizaole Compounds (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Description

United States Patent 3,254,094 3-lMINO-2,l-BENZISOTHIAZOLES Stephen T. Ross, Berwyn, Pa., assignor to Smith Kline &'
French Laboratories, Philadelphia, Pa., a corporation of Pennsylvania No Drawing. Filed Oct. 20, 1964, Ser. No. 405,251
8 Claims. (Cl. 260-304) structural formula:
E'|= s R Formula I in which:
R represents hydrogen, halogen of atomic weight less than 80 or trifluoromethyl, preferably the substituent is in the 5- or 6-position;
R represents hydrogen, lower alkyl or phenyl; and
R represents hydrogen or lower alkyl.
The term lower alkyl Where used herein signifies aliphatic groups of from one to four, preferably one to two, carbon atoms.
Advantageous compounds are represented by Formula I above when R is chlorine or trifiuoromethyl, preferably in position 5. I
A preferred compound is S-imino-l,3-dihydro-5-trifiuoromethyl-2,1-benzisothiazole.
This invention also includes salts of the above defined bases formed with nontoxic organic and inorganic acids. Such salts are easily prepared by methods known to the art. The base is reacted with either the calculated amount of organic or inorganic acid in aqueous miscible solvent, such as acetone or ethanol, with isolation of the salt by concentration and cooling or an excess of the acid in aqueous immiscible solvent, such 'as ethyl ether or chloroform, with the desired salt separating directly. Exemplary of such organic salts are those with ma-leic, hexamic, furnaric, benzoic, ascorbic, pamoic, succinic, bismethylenesalicylic, methanesulfonic, ethanedisulfonic, acetic, propionic, tartaric, salicylic, citric, gluconic, lactic, malic, mandelic, cinnamic, citraconic, aspartic, stearic, palmitic, itaconic, glycolic, p-aminobenzoic, glutamic, benzenesulfonic and the-ophylline acetic acids as well as with the 8-halotheophyllines, for example, 8-bromotheophylline. Exemplary of such inorganic salts are those with hydrochloric, hydrobromic, hydroiodic, sulfuric, sulfamic, phosphoric and nitric acids. Of course these salts may also be prepared by the classical method of double decomposition of .appropri the salts which is well-known to the art.
The imino benzisothiazoles of this invention are prepared by the following general procedure:
ice I Formula II wherein R R and R are as defined above. Thus, a 2- amino-benzthioamide as shown in Formula II is ring closed to form the 2,1-benzisothiazole using a mild oxidizing agent, for example potassium triiodide or a halogen: iodine, bromine or chlorine. Employing potassium triiodide, the reaction is advantageously carried out in an aqueous system, for example aqueous alcoholic solution such as methanol or ethanol at from 0-80 C., preferably at ambient or room temperature, for from 30 minutes to several hours. The reaction product is isolated as the hydroiodide salt of the 2,1-benzoisothiazole and if desired, the salt is treated with a weak inorganic or organic base to yield the benzisothiazole free base. of Formula I is hydrogen, sodium carbonate solution is employed to generate the free base. Further reaction with acids yields other salts as described hereinabove.
Employing a halogen (iodine, bromine or chlorine) as the mild oxidizing agent, the above reaction is advantageously carried out in a dilute solution using a suitable solvent which is unreactive toward the oxidizing agent, such as for example acetic acid, in a similar temperature range.
The Z-aminobenzthioamide starting materials used as described above are either known or are prepared by one of several procedures. to prepare the N-unsubstituted amido compounds of Formula II above:
Thus an anthanilonitrile is reacted with a mixture of liquid ammonia and gaseous hydrogen sulfide (ammonium sulfide) in an inert solvent such as Cellosolve, under pressure, for from four to eight hours to give upon workup the benzthioamide compound. The anthranilonitriles used as above are either known or are prepared by methods such as those set forth in the examples hereinbelow.
To prepare the N-substituted amido compound-s of Formula II the following procedure is used:
wherein R and R are as defined hereinabove and R is lower alkyl. Thus a 2-chlorobenzoyl halide (prepared from the corresponding carboxylic acid as set forth in the examples hereinbelow) is treated with a lower alkyl amine to yield the N-loweralkyl-Z-chlorobenza-mide which is reacted with ammonia or an amine in the presence of copper powder and a copper salt. The resulting N-lower alkyl-2-aminobenzamide is converted to the corresponding benzthioamide by the action of phosphorus pentasulfide.
The following examples illustrate in more detail the procedures for the preparation of the compounds of Formula I. It will be obvious to one skilled in the art that variations of these procedures may be employed to the same advantage. The specific compounds described in these examples is not intended to limit the scope of this invention which is defined by Formula I and the claims.
Preferably, when R The following procedure is used Example 1 A mixture of 648 g. of 4-chloro-3-cyanobenzotrifluoride, one liter of liquid ammonia, 4 g. cuprous chloride and 4 g. of copper powder is heated at 115-120 C. in a closed reactionvessel. The pressure climbs to 1030 pounds. The reaction vessel is washed with isopropanol and the filtered catalyst is washed with isopropanol and ether. The filtrate is concentrated and distilled to yield 5-trifluoromethylanthranilonitrile, B.P. 95-115 C./0.4 0.7 mm. The product recrystallizes from benzene and cyclohexane to melt at 7274 C.
Liquid ammonia (about ml.) is dissolved in 75 ml. of Cellosolve and gaseous hydrogen sulfide is passed in for 20 minutes at 5 C. A solution of 5.0 g. of the above 5-trifluoromethylanthrani-lonitrile in 10 ml, of Cellosolve is added and the mixture is placed in a glass bomb which is then heated in a steam bath with occasional shaking. After four hours the bomb is cooled and the contents is concentrated to dryness under reduced pressure. The residue is recrystallized from benzene-heptane to give 2 amino 5 trifluoromethylbenzthioamide, M.P. 119121 C.
The above thioamide (2.05 g.) is dissolved in a mixture of 50 ml. of methanol and 50 ml. of water. A solution of g. of potassium iodide and 2.36 g. of iodine in 50 ml. of water is added dropwise with stirring to the thioamide solution. The temperature is kept below 15 C. The mixture is stirred for two hours, then filtered to give 3- imino-1,3-dihydro 5 trifluoromethyl-Z,l-benzisothiazole hydroiodide. The free base is obtained by treating a methanolic solution of the hydroiodide with excess aqueous sodium carbonate solution. After recrystallization from benzene the free base product melts at 202- 203 C.
Example 2 To a solution of 6.0 g. of 2-aminobenzthioamide in 250 ml. of 50% aqueous methanol is added with stirring, a solution of 81 g. of potassium iodide and 10.0 g. of iodine in 250 ml. of water. The temperature is kept below 10 C. The mixture is stirred for one hour and filtered to give 3-imino-l,3-dihydro 2,1 benzisothiazole hydroiodide. methanolic solution of the hydroiodide with excess aqueous sodium carbonate solution. After recrystallization from ethanol the free base melts at 169.5171.5 C.
Example 3 To 21 g. of dry pyridine is added slowly with stirring, 23 g. of cuprous cyanide. The mixture rapidly solidifies and is then heated to 125 C. Excess pyridine is boiled off and the temperature decreased to 110 C. With stirring, 48 g. of 3-amino-4-bromobenzotrifiuoride is added slowly and the mixture heated to 165170 C. This temperature is maintained for 75 minutes and then the reac tion mixture is cooled to 90 C. A concentrated solution of sodium cyanide (75 .g. in 75 ml; of water) is added, followed by 250 ml. of benzene. The mixture is stirred for one hour and the separated benzene layer is washed with water, dried and evaporated. The residue is distilled at 122127 C. and 7.0 mm. to give 4-trifluoromethylanthranilonitrile which solidifies, melting at 86-89 C.
Following the-procedure of Example 1, 10.0 g. of the above 4-trifiuoromethylanthranilonitrile is reacted with ammonium sulfide in 75 ml. of Cellosolve to give 4-trifluoromethyl-Z-aminobenzthioamide, M.P. 102107 C. The thioamide (8.1 g.) thus prepared is reacted with an aqueous solution of 81 g. of potassium iodide and 9.35 g. of iodine. The reaction mixture is stirred for one hour and filtered to give'3-imino-1,3-dihydro-6-trifluoromethyl 2,1-benzisothiazole hydroiodide. The free base melts at 164.5166 C. upon recrystallization from benzene.
The free base is obtained by treating a 4 Example 4 trifluoromethylanthranilonitrile which solidified, M.P. 91-
A mixture of 5.0 g. of the above anthranilonitrile, 6.0.
g. of ammonium sulfide and 40 ml. of Cellosolve is heated in a pressure bottle at C. for five hours. The reaction mixture is cooled, filtered and the filtrate evaporated to dryness. The residue is taken up in hot cyclohexane, filtered and cooled to give 2-(N-phenylamino)-5- trifluoromethylbenzthioamide, M.P. 114115 C.
The above thioamide (4.3 g.) is dissolved in 200 ml. of methanol and an aqueous solution of potassium triiodide (3.70 g. of iodine and 40 g. of potassium iodide in 100 ml. of water) is added dropwise over 30 minutes. The reaction mixture is diluted with water and the precipitate filtered off to give 3-imino-1-phenyl-1,3-dihydro- 5-trifluoromethyl-2,1-benzisothiazole hydroiodide, M.P. 161-163 C. (d.).
Similarly, by employing 73 g. of N-ethylformamide instead of the formanilide in the above reaction and carrying the resulting N-ethyl-S-trifluoromethylanthranilonitrile through the ensuing procedures there is obtained the corresponding product, 3-imino-l-ethyl-l,3-dihydrO-5-trifluoromethyl-2,l-benzisothiazole hydroiodide.
Example 5 A mixture of g. of 4-chloro-3-cyanobenzotrifluoride, 70 g. of sodium hydroxide, 200 ml. of ethanol and 700 ml. of water is stirred at reflux for six and one-half hours. The solution is cooled, filtered and the filtrate extracted with ether and then benzene. The aqueous layer is treated with charcoal, refiltered and then acidified with excess hydrochloric acid to precipitate 2-chloro-5-trifluoromethylbenzoic acid, M.P. 92.5-95 C. This benzoic acid (108 g.) is stirred with 250 ml. of thionyl chloride for-one hour and refluxed for two hours. The excess thionyl chloride is distilled at the water pump and the residue distilled to give 2-chloro-S-trifluoromethylbenzoyl chloride, B.P. 113117 C./ca. 20 mm.
Ten grams of the above 2-chloro-5-trifluoromethylbenzoyl chloride in ether is treated with gaseous methyl amine for 30 minutes. The methylamine hydrochloride is filtered off and the filtrate evaporated to dryness to give N methyl 2-chloro-5-trifluoromethylbenzamide. This amide is dissolved in Cellosolve containing 10 g. of methylamine and 0.2 g. each of copper powder and copper sulfate is added. The mixture is heated at C. for 40 hours, cooled, filtered and the filtrate evaporated. The residue, N methyl-2-methylamino-5-trifluoromethylbenzamide, is dissolved in pyridine and 10 g. of phosphorus pentasulfide is added. This mixture is refluxed for one hour, then poured into water and filtered to give N-methyl-2-methylamino-5-trifiuoromethylbenzthioamide. After recrystallization from benzene, the above thioamide is dissolved in aqueous methanol and an equimolar quantity of iodine dissolved in an excess of aqueous potassium iodide solution is added. The resulting hydroiodide salt of 3 methylimino-l-methyl-l,3-dihydro-5-trifluoromethyl-2,l-benzisothiazole is filtered OE and the base generated by careful addition of aqueous sodium carbonate.
Example 6 Following the general procedure of Example 1, 4.1 g. of 5-chloroanthranilonitrile is reacted with ammonium sulfide (ammonia and hydrogen sulfide) in 75 ml. of Cellosolve under pressure to give 2-amino-5-chlorobenzthioamide. The thioamide thus prepared is reacted in aqueous methanol solution with an equimolar amount of iodine and an excess of potassium iodide. The reaction mixture is stirred at room temperature for one hour and then filtered to give 3-imino-1,3-dihydro-5-chloro-2,1- benzisothiazole hydroiodide. The free base is obtained by treating a methanolic solution of the hydroiodide with excess aqueous sodium carbonate solution.
Similarly, by following this procedure and employing 5.3 g. of S-bromoanthranilonitrile or 3.7 g. of 5-fluoroanthranilonitrile there is obtained 3-imino-1,3-dihydro- 5-bromo-2,1-benzisothiazole and 3-irnino-1,3-dihydro-5- fluoro-Z,l-benzisothiazole, respectively.
What is claimed is:
1. A chemical compound of the class consisting of a free base and its nontoxic, pharmaceutically acceptable acid addition salts, said free base having the formula:
wherein:
R is a member selected from the group consisting of hydrogen, halogen of atomic weight less than 80 and trifiuoromethyl; R is a member selected from the group consisting of hydrogen, lower alkyl of from 1 to 4 carbon atoms and.
phenyl; and R is a member selected from the group consisting of hydrogen and lower alkyl of from 1 to 4 carbon atoms.
2. A chemical compound of the formula:
=NH |S CFQ 3. A chemical compound of the formula:
C F 3- =NH 4. A chemical compound of the formula:
5. A chemical compound of the formula:
6. A chemical compound of the formula:
7. A chemical compound of the formula:
C F 3 I=NH 8. The method of preparing 3-imino-2,l-benzisothiazole hydroiodide salts of the formula:
wherein which comprises oxidizing with potassium triiodide a benzthioamide of the formula:
wherein R R and R are as defined above.
References Cited by the Examiner UNITED STATES PATENTS 2,032,465 3/1936 Bradley et al. 260*465 2,803,640 8/1957 Heckert 260465 3,014,041 12/1961 Hausermann et al. M. 260304 3,170,955 2/1965 Richards et al. 260558 3,178,475 4/1965 Schmidt et al. 260558 3,187,001 6/1965 Meyer et al. 260304 NICHOLAS S. RIZZO, Primary Examiner.
HENRY R. JILES, Examiner.
ALTON D. ROLLINS, Assistant Examiner.

Claims (2)

1. A CHEMICAL COMPOUND OF THE CLASS CONSISTING OF A FREE BASE AND ITS NONTOXIC, PHARMACEUTICALLY ACCEPTABLE ACID ADDITION SALTS, SAID FREE BASE HAVING THE FORMULA:
8. THE METHOD OF PREPARING 3-IMINO-2,1-BENZISOTHAIAZOLE HYDROIODIDE SALTS OF THE FORMULA:
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Cited By (6)

* Cited by examiner, † Cited by third party
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US3682941A (en) * 1967-03-18 1972-08-08 Basf Ag Production of 1,2-benzoisothiazoles
US4140692A (en) * 1976-03-10 1979-02-20 Basf Aktiengesellschaft Manufacture of 3-amino-1,2-benzisothiazoles
US20030045741A1 (en) * 2001-06-13 2003-03-06 Ben-Zion Dolitzky Novel process for preparing rac-bicalutamide and its intermediates
US7102026B2 (en) 2001-06-13 2006-09-05 Teva Gyógyszergyár Zártkörüen Müködö Részvénytársaság Process for preparing and isolating rac-bicalutamide and its intermediates
EP2423188A1 (en) * 2003-08-29 2012-02-29 Mitsui Chemicals Agro, Inc. Agricultural/Horticultural Insecticide and Method for Using the Same
CN110845434A (en) * 2019-11-28 2020-02-28 河北嘉泰化工科技有限公司 Continuous salt-free environment-friendly preparation method of scarlet powder

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CA1157884A (en) * 1980-04-16 1983-11-29 Byron R. Cotter Process for the preparation of trifluoromethylbenzoyl halides

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US2032465A (en) * 1931-07-10 1936-03-03 Ici Ltd Amino-hydroxy-naphthonitriles and processes of preparing same
US2803640A (en) * 1954-11-12 1957-08-20 Du Pont Alpha-cyanovinyl-substituted aryl amines and their preparation
US3014041A (en) * 1958-06-19 1961-12-19 Geigy Ag J R Heterocyclic substituted coumarin colours
US3170955A (en) * 1958-04-25 1965-02-23 Abbott Lab Amino and halogen substituted-n-diloweralkylamino-alkyl-benzamides
US3178475A (en) * 1961-09-05 1965-04-13 Ciba Geigy Corp Benzoyl guanidines
US3187001A (en) * 1963-07-22 1965-06-01 Parke Davis & Co Certain 2, 1-benzisothiazole compounds

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Publication number Priority date Publication date Assignee Title
US2032465A (en) * 1931-07-10 1936-03-03 Ici Ltd Amino-hydroxy-naphthonitriles and processes of preparing same
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US3682941A (en) * 1967-03-18 1972-08-08 Basf Ag Production of 1,2-benzoisothiazoles
US4140692A (en) * 1976-03-10 1979-02-20 Basf Aktiengesellschaft Manufacture of 3-amino-1,2-benzisothiazoles
US20030045741A1 (en) * 2001-06-13 2003-03-06 Ben-Zion Dolitzky Novel process for preparing rac-bicalutamide and its intermediates
WO2002100339A3 (en) * 2001-06-13 2003-10-16 Biogal Gyogyszergyar Novel process for preparing rac-bicalutamide and its intermediates
US20040059147A1 (en) * 2001-06-13 2004-03-25 Ben-Zion Dolitzky Novel process for preparing rac-bicalutamide and its intermediates
US6737550B2 (en) 2001-06-13 2004-05-18 Biogal Gryogyszergyar Rt. Process for preparing rac-bicalutamide and its intermediates
US20040167349A1 (en) * 2001-06-13 2004-08-26 Ben-Zion Dolitzky Novel process for preparing rac-bicalutamide and its intermediates
US20040176638A1 (en) * 2001-06-13 2004-09-09 Ben-Zion Dolitzky Novel process for preparing rac-bicalutamide and its intermediates
US20040176633A1 (en) * 2001-06-13 2004-09-09 Ben-Zion Dolitzky Novel process for preparing rac-bicalutamide and its intermediates
US6797843B2 (en) 2001-06-13 2004-09-28 BIOGAL Gyógyszergyár Rt. Process for preparing rac-bicalutamide and its intermediates
US6849763B2 (en) 2001-06-13 2005-02-01 BIOGAL Gyógyszergyár Rt. Process for preparing rac-bicalutamide and its intermediates
US6861557B2 (en) 2001-06-13 2005-03-01 BIOGAL Gyógyszergyár Rt. Process for preparing rac-bicalutamide and its intermediates
US20050090682A1 (en) * 2001-06-13 2005-04-28 Ben-Zion Dolitzky Novel process for preparing rac-bicalutamide and its intermediates
US7102026B2 (en) 2001-06-13 2006-09-05 Teva Gyógyszergyár Zártkörüen Müködö Részvénytársaság Process for preparing and isolating rac-bicalutamide and its intermediates
EP2423188A1 (en) * 2003-08-29 2012-02-29 Mitsui Chemicals Agro, Inc. Agricultural/Horticultural Insecticide and Method for Using the Same
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US8816128B2 (en) 2003-08-29 2014-08-26 Mitsui Chemicals, Inc. Insecticide for agricultural or horticultural use and method of use thereof
US9089133B2 (en) 2003-08-29 2015-07-28 Mitsui Chemicals, Inc. Insecticide for agricultural or horticultural use and method of use thereof
US9101135B2 (en) 2003-08-29 2015-08-11 Mitsui Chemicals, Inc. Agricultural/horticultural insecticide and method for using the same
CN102718665B (en) * 2003-08-29 2015-09-16 三井化学株式会社 Insecticide for agricultural or horticultural use prepare intermediate
CN110845434A (en) * 2019-11-28 2020-02-28 河北嘉泰化工科技有限公司 Continuous salt-free environment-friendly preparation method of scarlet powder

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